US4289774A - Lipid lowering and anti-thrombotic 6-arylpyridazin-3-ones and a process for their preparation - Google Patents
Lipid lowering and anti-thrombotic 6-arylpyridazin-3-ones and a process for their preparation Download PDFInfo
- Publication number
- US4289774A US4289774A US06/086,604 US8660479A US4289774A US 4289774 A US4289774 A US 4289774A US 8660479 A US8660479 A US 8660479A US 4289774 A US4289774 A US 4289774A
- Authority
- US
- United States
- Prior art keywords
- biphenylyl
- methyl
- tetrahydropyridazin
- fluoro
- dihydropyridazin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/04—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having less than three double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/14—Oxygen atoms
Definitions
- the present invention relates to 6-arylpyridazin-3-ones having pharmacological properties and to a process for the preparation thereof.
- R 1 is 4-biphenylyl or 4-phenoxyphenyl, both of which may be unsubstituted or substituted in the 4'-position by F, Cl, Br or I;
- R 2 is H, alkyl or hydroxyalkyl, each of 1-4 carbon atoms, or pyridyl;
- R 3 and R 6 are each H or alkyl of 1-4 carbon atoms, or together are --(CH 2 ) 4 --; and
- R 4 and R 5 are each H or together are a C--C bond; but at least one of the radicals R 2 , R 3 and R 6 is other than hydrogen.
- R 1 is preferably 4-biphenylyl, 4'-fluoro-4-biphenylyl or 4-p-chlorophenoxyphenyl, and also preferably 4'-chloro-4-biphenylyl, 4'-bromo-4-biphenylyl, p-phenoxyphenyl, 4-p-fluorophenoxyphenyl or 4-p-bromophenoxyphenyl.
- the alkyl group is preferably methyl, but also can be ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl or tert-butyl.
- hydroxyalkyl is preferably 2-hydroxyethyl, but also can be, for example, 1-hydroxyethyl, 1-, 2- or 3-hydroxypropyl or 1-, 2-, 3- or 4-hydroxybutyl.
- Pyridyl is preferably pyrid-2-yl, but also can be pyrid-3-yl or pyrid-4-yl.
- R 2 is preferably H, methyl, 2-hydroxyethyl or pyrid-2-yl.
- R 3 and R 6 are preferably each H or methyl or together are --(CH 2 ) 4 --.
- R 4 and R 5 are preferably each H.
- One of the radicals R 2 , R 3 and R 6 must be other than hydrogen. Furthermore, those compounds of Formula I in which one or two of these radicals are hydrogen are preferred.
- the invention particularly relates to those compounds of Formula I in which at least one of the defined radicals has one of the preferred meanings given above.
- the invention further relates to a process for the preparation of the 6-arylpyridazin-3-ones of Formula I, which comprises:
- R 1 and R 3 to R 6 are as defined for Formula I, or a reactive derivative of the carboxylic acid with a hydrazine of Formula III
- R 2 is as defined for Formula I; or, optionally,
- the preparation of the compounds of Formula I is carried out in accordance with procedures known per se, as described in the literature (for example, in the standard works such as Houben-Weyl, Methoden der Organischen Chemie (Methods of Organic Chemistry), Georg-Thieme-Verlag, Stuttgart), and under reaction conditions which are also well-known, and suitable, for these reactions. In these reactions, variants which are known per se but are not mentioned in more detail herein may also be utilized.
- keto-acids of Formula II can be prepared in accordance with methods known per se, for example, by reacting biphenyls or diphenyl ethers of the formula R 1 --H with anhydrides of dicarboxylic acids of the formula HOOC--CR 5 R 6 --CR 3 R 4 --COOH by the Friedel-Crafts method in the presence of AlCl 3 .
- reactive derivatives thereof may also be employed in the reaction of this invention.
- Particularly suitable derivatives include esters, for example, the alkyl esters, wherein the alkyl group preferably is of 1-4 carbon atoms, especially the methyl esters and ethyl esters.
- the acid halides of the acids of Formula II for example, the acid chlorides or acid bromides.
- Other suitable reactive derivatives of the carboxylic acids of Formula II can be conventionally formed in situ during the reaction, without being isolated.
- the other starting materials can, if desired, also be formed in situ, so that they are not isolated from the reaction mixture and instead are directly reacted further to produce the compounds of Formula I.
- suitable inert solvents include alcohols, e.g., methanol, ethanol, isopropanol, n-butanol, isoamyl alcohol; glycols and their ethers, e.g., ethylene glycol, diethylene glycol, ethylene glycol monomethyl ether and ethylene glycol monoethyl ether (methylglycol and ethylglycol); as well as ethers, especially water-soluble ethers, e.g., tetrahydrofuran, dioxane or ethylene glycol dimethyl ether (diglyme); and also water; and mixtures of these solvents with one another, especially mixtures with water, for example, aqueous ethanol.
- alcohols e.g., methanol, ethanol, isopropanol, n-butanol, isoamyl alcohol
- glycols and their ethers e.g., ethylene glycol, diethylene glycol, ethylene glycol mono
- the reaction temperatures are advantageously approximately 20°-approximately 200° C., preferably 60°-100° C., and the reaction times are approximately 1-48 hours.
- the dehydrogenation is advantageously carried out by treatment with bromine, preferably using a carboxylic acid, e.g., acetic acid, as the solvent and carrying out the process at an elevated temperature (about 40° to 120° C.).
- a carboxylic acid e.g., acetic acid
- the bromination product first formed (presumably corresponding to Formula I, but with Br in place of R 4 or R 5 ) is not isolated; instead, the selected reaction conditions suffice to cause its dehydrobromination to the desired dihydropyridazinone.
- the compounds of Formula I can possess one or more centers of asymmetry. They can therefore be obtained from their process of preparation as racemates, or, if optically active starting materials are used, also in an optically active form. If the compounds have two or more centers of asymmetry, they are in general obtained from the syntheses as mixtures of racemates, from which the individual racemates can be isolated in the pure form, for example, by recrystallization from inert solvents. The racemates obtained can, if desired, be separated mechanically or chemically into their optical antipodes by methods known per se.
- the compounds of Formula I combine good acceptability by the patient with valuable pharmacological properties.
- they exhibit an anti-arteriosclerotic effect and an effect in lowering the lipid level.
- they lower the cholesterol level (demonstrable in the serum of rats by the method of Levine et al, Automation in Analytical Chemistry, Technicon Symposium 1967, Mediad, N.Y., pages 25-28) and lower the level of triglycerides (demonstrable by the method of Noble and Campbell, Clin. Chem. 16 (1970), pages 166-170).
- anti-thrombotic above all thrombocyte aggregation-inhibiting properties, are displayed.
- the effect on the thrombocyte function i.e., the inhibition of aggregation, can be demonstrated on rabbits in the Born test in vitro and ex vivo (Nature, 194 (1962), pages 927-929) and in the Jacobi fiber test (Thrombos. Diathes. haemorrh. 26 (1971), pages 192-202). Furthermore, antiphlogistic, fibrinolytic, blood sugar-lowering and analgesic properties, as well as effects on the central nervous system, are found, and can be determined in accordance with conventional methods used for these activities.
- the compounds of Formula I can therefore be used as medicaments in human medicine and veterinary medicine. Further, they can be used as intermediate products for the preparation of other active ingredients of medicaments.
- this invention further relates to the use of the compounds of Formula I for the preparation of pharmaceutical formulations, especially by non-chemical methods.
- the compounds, together with one or more solid, liquid or semi-liquid excipients or auxiliaries, and with or without one or more additional active ingredients, can be converted into a suitable dosage form.
- this invention further relates to agents, especially pharmaceutical formulations, which contain a compound of Formula I.
- formulations may be used as medicaments in human medicine or verterinary medicine.
- Appropriate excipients include organic or inorganic substances which are suitable for enteral (for example, oral) or parenteral administration or for topical application and which do not react with the novel compounds, for example, water, vegetable oils, benzyl alcohols, polyethylene glycols, glycerol triacetate, gelatine, carbohydrates, such as lactose or starch, magnesium stearate, talc and vaseline.
- Tablets, dragees, capsules, syrups, elixirs or drops are in particular employed for oral use, suppositories for rectal use, solutions, preferably oily or aqueous solutions, as well as suspensions, emulsions or implants, for parenteral use, and ointments, creams or powders for topical use.
- the packaging materials such as paper sachets or paper capsules, are also suitable excipients.
- the novel compounds can also be lyophilized and the resulting lyophilizates used, for example, for the preparation of injection formulations.
- the formulations mentioned can be sterilized and/or contain auxiliaries, such as lubricants, preservatives, stabilizers and/or wetting agents, emulsifiers, salts for influencing the osmotic pressure, buffer substances, dyestuffs, flavorings and/or scents. They can, if desired, also contain one or more additional active ingredients, for example, one or more vitamins.
- auxiliaries such as lubricants, preservatives, stabilizers and/or wetting agents, emulsifiers, salts for influencing the osmotic pressure, buffer substances, dyestuffs, flavorings and/or scents.
- auxiliaries such as lubricants, preservatives, stabilizers and/or wetting agents, emulsifiers, salts for influencing the osmotic pressure, buffer substances, dyestuffs, flavorings and/or scents.
- additional active ingredients for example, one or more vitamins.
- This invention in another aspect, further relates to the use of the compounds of Formula I in the therapeutic treatment of humans or animals and in combating diseases.
- the compounds of Formula I are suitable for the treatment and/or prophylaxis of disease symptoms entailing increased serum lipids and increased tendency to thrombosis, of primary and secondary hyperlipoproteinaemias with or without xanthomatosis, of arteriosclerosis (coronary sclerosis, cerebral sclerosis and peripheral vascular sclerosis), and of diabetic angiopathies (diabetic retinopathy).
- the substances according to this invention are as a rule administered analogously to known, commercially available lipid-lowering agents (e.g., Clofibrat), preferably in dosages of approximately 10-1,000 mg, especially 50-500 mg, per dosage unit.
- the daily dosage is preferably approximately 0.2-100 mg/kg of body weight.
- the particular dose for each individual patient depends, however, on a great diversity of conventional factors, for example, on the activity of the special compound employed, on the age, body weight, general condition of health and sex of the subject, on the cost, on the time and method of administration, on the rate of excretion, on the combination of medicaments administered and on the severity of the particular disease for which the therapy is intended. Oral administration is preferred.
- Tablets are pressed analogously to Example A and are subsequently coated in the conventional manner with a coating of sucrose, potato starch, talc, tragacanth and dyestuff.
- Tablets, dragees and capsules which contain one or more of the other active ingredients of Formula I may be obtained analogously.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Obesity (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19782845456 DE2845456A1 (de) | 1978-10-19 | 1978-10-19 | 6-arylpyridazin-3-one und verfahren zu ihrer herstellung |
DE2845456 | 1978-10-19 |
Publications (1)
Publication Number | Publication Date |
---|---|
US4289774A true US4289774A (en) | 1981-09-15 |
Family
ID=6052528
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/086,604 Expired - Lifetime US4289774A (en) | 1978-10-19 | 1979-10-19 | Lipid lowering and anti-thrombotic 6-arylpyridazin-3-ones and a process for their preparation |
Country Status (12)
Country | Link |
---|---|
US (1) | US4289774A (de) |
EP (1) | EP0010156B1 (de) |
JP (1) | JPS5557570A (de) |
AT (1) | ATE1624T1 (de) |
AU (1) | AU532749B2 (de) |
CA (1) | CA1134826A (de) |
DE (2) | DE2845456A1 (de) |
ES (1) | ES485153A1 (de) |
HU (1) | HU180264B (de) |
IL (1) | IL58473A (de) |
YU (1) | YU252479A (de) |
ZA (1) | ZA795561B (de) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4631279A (en) * | 1984-10-15 | 1986-12-23 | Eli Lilly And Company | 6-(pyridinylphenyl)dihydropyridazinones as inotropic agents |
US4667033A (en) * | 1983-06-10 | 1987-05-19 | A. Nattermann & Cie Gmbh | Substituted 6-(thien-2-yl)-3(2H)-pyridazinones |
WO1989000567A1 (en) * | 1987-07-22 | 1989-01-26 | Rorer International (Overseas) Inc. | Benzopyridazinone and pyridopyridazinone compounds and their use in the treatment of congestive heart failure |
US5151420A (en) * | 1988-10-19 | 1992-09-29 | Orion Corporation/Orion Pharmaceutica | Substituted pyridazinones |
US6103718A (en) * | 1997-01-15 | 2000-08-15 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phthalazinones |
US6399611B1 (en) | 1995-04-20 | 2002-06-04 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Arylalkylpyridazinones |
US7074959B2 (en) * | 2002-08-01 | 2006-07-11 | New Mexico Highlands University | Methods and systems for remediating hydrazine-contaminated equipment and/or surfaces |
US9296741B2 (en) | 2011-12-30 | 2016-03-29 | Abbvie Inc. | Bromodomain inhibitors |
US9561231B2 (en) | 2012-06-12 | 2017-02-07 | Abbvie Inc. | Pyridinone and pyridazinone derivatives |
US10633379B2 (en) | 2016-04-15 | 2020-04-28 | Abbvie Inc. | Bromodomain inhibitors |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3124699A1 (de) * | 1981-06-24 | 1983-01-13 | Basf Ag, 6700 Ludwigshafen | Neue 2-aryl-3,4-diaza-bicyclo(4.n.0.)alken-(2)-one-(5),verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
EP0210530A1 (de) * | 1985-07-27 | 1987-02-04 | MERCK PATENT GmbH | 6-Arylalkenylpyridazinone |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3682914A (en) * | 1967-11-22 | 1972-08-08 | Hisao Yamamoto | 2,6-diphenyl-4,5-dihydro-3(2h)-pyridizinone derivatives |
US3689652A (en) * | 1970-10-09 | 1972-09-05 | William Vincent Curran | Method of lowering blood pressure in mammals |
US3812256A (en) * | 1971-06-08 | 1974-05-21 | American Cyanamid Co | Novel method for lowering blood pressure in mammals |
US3822260A (en) * | 1970-10-09 | 1974-07-02 | American Cyanamid Co | 6-(cyanophenyl)-4,5-dihydro-3(2h)-pyridazinones |
US3931177A (en) * | 1973-12-19 | 1976-01-06 | Smith Kline & French Laboratories, Inc. | 6-(3-Substituted amino-2-hydroxypropoxyaryl)-4,5-dihydro-3(2H)-pyridazinones |
US4088762A (en) * | 1971-02-22 | 1978-05-09 | Bdh Pharmaceuticals Limited | 6-(P-PIPERAZINO)-PHENYL-4,5-DIHYDRO-3(2H)pyridazinones |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1670683A1 (de) * | 1966-03-31 | 1970-01-02 | Bayer Ag | Verfahren zur Herstellung neuartiger Arylaether |
GB1383906A (en) * | 1971-02-22 | 1974-02-12 | Bdh Pharmaceuticals Ltd | Pyridazinones |
US3840662A (en) * | 1971-08-05 | 1974-10-08 | Shimamoto Takio | Method of treating atherosclerosis using 4-hydroxymethyl-1-keto-1,2-dihydrophthalazine or acid salts thereof |
JPS6037101B2 (ja) * | 1977-03-09 | 1985-08-24 | 三共株式会社 | フエニルピリダジノン誘導体の製法 |
-
1978
- 1978-10-19 DE DE19782845456 patent/DE2845456A1/de not_active Withdrawn
-
1979
- 1979-09-12 DE DE7979103396T patent/DE2963814D1/de not_active Expired
- 1979-09-12 EP EP79103396A patent/EP0010156B1/de not_active Expired
- 1979-09-12 AT AT79103396T patent/ATE1624T1/de not_active IP Right Cessation
- 1979-10-16 IL IL58473A patent/IL58473A/xx unknown
- 1979-10-17 YU YU02524/79A patent/YU252479A/xx unknown
- 1979-10-18 CA CA000337906A patent/CA1134826A/en not_active Expired
- 1979-10-18 AU AU51933/79A patent/AU532749B2/en not_active Ceased
- 1979-10-18 ES ES485153A patent/ES485153A1/es not_active Expired
- 1979-10-18 ZA ZA00795561A patent/ZA795561B/xx unknown
- 1979-10-19 US US06/086,604 patent/US4289774A/en not_active Expired - Lifetime
- 1979-10-19 JP JP13428379A patent/JPS5557570A/ja active Pending
- 1979-10-19 HU HU79ME2311A patent/HU180264B/hu unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3682914A (en) * | 1967-11-22 | 1972-08-08 | Hisao Yamamoto | 2,6-diphenyl-4,5-dihydro-3(2h)-pyridizinone derivatives |
US3689652A (en) * | 1970-10-09 | 1972-09-05 | William Vincent Curran | Method of lowering blood pressure in mammals |
US3822260A (en) * | 1970-10-09 | 1974-07-02 | American Cyanamid Co | 6-(cyanophenyl)-4,5-dihydro-3(2h)-pyridazinones |
US4088762A (en) * | 1971-02-22 | 1978-05-09 | Bdh Pharmaceuticals Limited | 6-(P-PIPERAZINO)-PHENYL-4,5-DIHYDRO-3(2H)pyridazinones |
US3812256A (en) * | 1971-06-08 | 1974-05-21 | American Cyanamid Co | Novel method for lowering blood pressure in mammals |
US3931177A (en) * | 1973-12-19 | 1976-01-06 | Smith Kline & French Laboratories, Inc. | 6-(3-Substituted amino-2-hydroxypropoxyaryl)-4,5-dihydro-3(2H)-pyridazinones |
Non-Patent Citations (6)
Title |
---|
Child et al., J. Pharm Sci 66, 466 (1977). * |
Curran IV, J. Med. Chem. 17, 273 (1974). * |
Fateen et al., Chem. Abs. 70, 3997m (1967). * |
Fateen et al., J. Chem. U.A.R. 10, 321 (1967). * |
Kulkarni, Current Science 46, 801-3 (1977). * |
Pitarch et al., European J. Med. Chem. 9, 644 (1974). * |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4667033A (en) * | 1983-06-10 | 1987-05-19 | A. Nattermann & Cie Gmbh | Substituted 6-(thien-2-yl)-3(2H)-pyridazinones |
US4631279A (en) * | 1984-10-15 | 1986-12-23 | Eli Lilly And Company | 6-(pyridinylphenyl)dihydropyridazinones as inotropic agents |
WO1989000567A1 (en) * | 1987-07-22 | 1989-01-26 | Rorer International (Overseas) Inc. | Benzopyridazinone and pyridopyridazinone compounds and their use in the treatment of congestive heart failure |
US4806535A (en) * | 1987-07-22 | 1989-02-21 | Rorer Pharmaceutical Corporation | Imidazolylphenyl and 1,2,4-triazolylphenyl benzopyridazinone and pyridopyridazinone compounds and their use for increasing cardiatonic contractility |
US5151420A (en) * | 1988-10-19 | 1992-09-29 | Orion Corporation/Orion Pharmaceutica | Substituted pyridazinones |
US6399611B1 (en) | 1995-04-20 | 2002-06-04 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Arylalkylpyridazinones |
US6531473B2 (en) | 1995-04-20 | 2003-03-11 | Merck Patent Gmbh | Method of treatment using arylalkylpyridazinones |
US6103718A (en) * | 1997-01-15 | 2000-08-15 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phthalazinones |
US7074959B2 (en) * | 2002-08-01 | 2006-07-11 | New Mexico Highlands University | Methods and systems for remediating hydrazine-contaminated equipment and/or surfaces |
US9296741B2 (en) | 2011-12-30 | 2016-03-29 | Abbvie Inc. | Bromodomain inhibitors |
US9561231B2 (en) | 2012-06-12 | 2017-02-07 | Abbvie Inc. | Pyridinone and pyridazinone derivatives |
US10633379B2 (en) | 2016-04-15 | 2020-04-28 | Abbvie Inc. | Bromodomain inhibitors |
Also Published As
Publication number | Publication date |
---|---|
EP0010156A1 (de) | 1980-04-30 |
ZA795561B (en) | 1980-09-24 |
ATE1624T1 (de) | 1982-10-15 |
IL58473A (en) | 1985-07-31 |
HU180264B (en) | 1983-02-28 |
JPS5557570A (en) | 1980-04-28 |
AU5193379A (en) | 1980-04-24 |
YU252479A (en) | 1983-01-21 |
AU532749B2 (en) | 1983-10-13 |
DE2963814D1 (en) | 1982-11-11 |
EP0010156B1 (de) | 1982-10-06 |
DE2845456A1 (de) | 1980-08-14 |
CA1134826A (en) | 1982-11-02 |
IL58473A0 (en) | 1980-01-31 |
ES485153A1 (es) | 1980-05-16 |
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